Spain pushes limits in administration of second dose of AstraZeneca

BarcelonaMore than 200,000 people in Catalonia - 2 million throughout the State - aged between 18 and 59 years received the first dose of the AstraZeneca vaccine in early February. Now, two months later, they are waiting for the Ministry of Health to find out how they will complete immunisation: they do not know if they will be able to finish the vaccination with AstraZeneca, if they will have to receive a second injection from Pfizer -the preferred option by the Ministry- or whether they will have to stick to only one dose, which promises 70% protection. Essential groups such as pharmacists, physiotherapists, teachers and police officers are living in an information limbo.

AstraZeneca's data sheet states that the schedule must be completed with two doses spaced a minimum of four weeks and a maximum of ten to twelve weeks apart to achieve maximum protection. The identification of some "infrequent and very rare" cases of thrombosis among young vaccine recipients, however, led Spain in early April to become one of the countries that limited the use of this vaccine exclusively to the 60 to 69 age group. It also suspended the inoculation of second doses to younger people because it feared they would develop health problems associated with the vaccine.

And the position has been firm: the State has chosen to refuse to administer the second doses of AstraZeneca to the under-60s, in line with other European countries, such as France and Germany. All this, despite the fact that the European Medicines Agency (EMA) itself recommends following the original schedule - two doses in twelve weeks - rather than injecting them with another vaccine or no vaccine at all.

"The Spanish criterion goes against a very clear recommendation by the EMA, who are the experts and the technical body that should guide countries' actions. The fact we are still not sure about what to do or subjecting an important public health decision to a study with 600 participants, when there are larger and better designed studies in the world that support its use, can only respond to a political, not scientific motivation", says Quique Bassat, epidemiologist and researcher Icrea at the Institute for Global Health in Barcelona (ISGlobal), a center promoted by the Fundació La Caixa.

The expert is referring to the clinical trial being carried out by the Carlos III Health Institute (ISCIII) through five hospitals - Vall d'Hebron and Hospital Clínic, in Catalonia; La Paz and Hospital Clínic San Carlos, in Madrid, and Hospital Cruces, in the Basque Country - to test the safety and efficacy of administering a second dose of Pfizer to those younger than 60 who received AstraZeneca. This study, called CombiVacs, will measure the amount of antibodies generated and its neutralising capacity - that is, to block the entry of the virus into human cells - to confirm that the combination of vaccines can increase the production of defenses against covid.

The results of the study, however, will not be made public for "four to five weeks" and will probably mean that the recommended 12 weeks between the two doses will be exceeded in the case of those who first received the vaccine. "It will not be a problem of being late, because it is better to administer the second dose sixteen weeks later than not to administer it," admits Bassat. And, in fact, with the provisional results of the trial, which will be known in early May, there would still be time to meet the deadlines with people who are awaiting the second injection. The problem, Bassat insists, is that a study with such a small sample cannot be considered the key to rolling out a vaccination strategy. And even more so considering that AstraZeneca is the most widely used vaccine in the world, the one with the lowest cost and the one that is easiest to store.

"Domino effect" in Europe

The combination of vaccines is a risky bet, according to the World Health Organization (WHO), since not enough evidence has been generated regarding the suitability of mixing adenovirus and messenger RNA vaccines, although there have been some experimental trials with animals. However, it is the option that has the most supporters in the technical committee of the Spanish Ministry of Health, along with immunisation with a single dose, since in both cases there would be a protection of more than 70%

"But combining vaccines would not be so much a problem of efficacy as of safety: it would be a mistake to change a guideline endorsed by a regulatory agency with such strict standards as the EMA and invent a different one by mixing vaccines. We do not know if this would cause more damage than we are trying to avoid," laments Bassat. According to the epidemiologist, the problem is that Spain has no intention of reviewing its decision regarding AstraZeneca despite the EMA urging to intensify its use.

The expert says that this change of criteria responds mainly to a "domino effect" between countries. "They do not want to administer the second doses because, directly, they do not want to administer this vaccine and make up arguments such as for example whatever answer the study gives them, which they will use to camouflage a purely political decision," he laments. In this sense, Bassat believes that it is a "political punishment disguised as a scientific decision" by the European countries for the problems in distribution, which have led the European Commission to take the Anglo-Swedish producer to court.